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Formalin tissue fixation biases myelin‐sensitive MRI
Journal article   Peer reviewed

Formalin tissue fixation biases myelin‐sensitive MRI

Alan C Seifert, Melissa Umphlett, Marco Hefti, Mary Fowkes and Junqian Xu
Magnetic resonance in medicine, Vol.82(4), pp.1504-1517
10/2019
DOI: 10.1002/mrm.27821
PMCID: PMC6626568
PMID: 31125149
url
https://www.ncbi.nlm.nih.gov/pmc/articles/6626568View
Open Access

Abstract

Purpose Chemical fixatives such as formalin form cross‐links between proteins and affect the relaxation times and diffusion properties of tissue. These fixation‐induced changes likely also affect myelin density measurements produced by quantitative magnetization transfer and myelin water imaging. In this work, we evaluate these myelin‐sensitive MRI methods for fixation‐induced biases. Methods We perform quantitative magnetization transfer, myelin water imaging, and deuterium oxide‐exchanged zero TE imaging on unfixed human spinal cord tissue at 9.4 Tesla and repeat these measurements after 1 day and 31 days of formalin fixation. Results The quantitative magnetization‐transfer bound pool fraction increased by 30.7% ± 21.1% after 1 day of fixation and by 42.6% ± 33.9% after 31 days of fixation. Myelin water fraction increased by 39.7% ± 15.5% and 37.0% ± 15.9% at these same time points, and mean T2 of the myelin water pool nearly doubled. Reference‐normalized deuterium oxide‐exchanged zero TE signal intensity increased by 8.17% ± 6.03% after 31 days of fixation but did not change significantly after 1 day of fixation. After fixation, specimen cross‐sectional area decreased by approximately 5%; after correction for shrinkage, changes in deuterium oxide‐exchanged zero TE intensity were nearly eliminated. Conclusion Bound pool fraction and myelin water fraction are significantly increased by formalin fixation, whereas deuterium oxide‐exchanged zero TE intensity is minimally affected. Changes in quantitative magnetization transfer and myelin water imaging may be due in part to delamination and formation of vacuoles in the myelin sheath. Deuterium oxide‐exchanged signal intensity may be altered by fixation‐induced changes in myelin lipid solid‐state 1H T1. We urge caution in the comparison of these measurements across subjects or specimens in different states, especially unfixed versus fixed tissue.
 myelin quantitative magnetization transfer (qMT) MRI myelin water imaging (MWI) zero TE (ZTE) imaging formalin fixation

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